It is the primary objective of this research program to determine the cause of photoreceptor degeneration in the inherited disease of rd mice and RCS rats. We intend to realize our objective by systematically investigating the mechanisms by which abnormalities in cGMP metabolism initiate visual cell degeneration in the genetically induced diseases of mice and rats and in drug-induced pathology of normal retinas in Xenopus laevis eye rudiment culture. We will study the biochemical regulation of cGMP metabolism in visual cells and evaluate whether cGMP concentration changes can regulate the content of specific, biologically active phosphoproteins. Work will also be continued with RCS retinas to define the biochemical relationship between membranous debis that forms from an error in pigment epithelium function and cGMP metabolism in RCS visual cells. It is envisioned that an understanding of how cGMP modulates the metabolism or function of normal visual cells will provide insight into how it may act to disrupt the homeostatic balance of rd and RCS visual cells to initiate the degenerative process.